CYSLTR1 Membrane Protein Introduction

Introduction of CYSLTR1

CYSLTR1, encode by CYSLTR1 gene, belongs to the G protein-coupled receptor family which has seven transmembrane domains. It is widely expressed in many human tissues, such as urinary bladder, spleen, lymph node, gallbladder, esophagus, appendix and so on. Recently, most studies have shown that CYSLTR1 plays an essential role in multiple metabolic activities, involved in the mediation of inflammatory reaction and tumors progression.

Function of CYSLTR1 Membrane Protein

CYSLTR1 is a receptor for cysteinyl leukotrienes. The receptor interaction with its ligand can activate a phosphatidylinositol-calcium second messenger system involving in mediating bronchoconstriction. Moreover, the activated receptor is also associated with contraction and proliferation of bronchial smooth muscle cells and eosinophil migration. Besides, activated CYSLTR1 by leukotrienes produced in leukocytes can regulate a variety of allergic and hypersensitivity reactions in humans. CYSLTR1 in endothelial cells translocate to the nucleus in a ligand-independent manner after ischemic insult in vitro, and it is involved in the ischemic injury. Additionally, a lot of studies showed that the abnormal expression of CYSLTR1 is associated with the progression of multiple types of cancer and asthma. Overexpression of CYSLTR1 has been observed in prostate cancer, renal cell carcinoma, transitional cell carcinoma and colorectal. These also implicate that CYSLTR1 antagonists can be used as an effective therapeutic method for cancer and asthma.

Fig.1 The roles of leukotrienes and acetylation in the expression of pro-inflammatory mediators through the NF-κB pathway. (Wisastra, 2014)

Application of CYSLTR1 Membrane Protein in Literature

1. Rabinovitch N., et al. Cysteinyl leukotriene receptor 1 and health effects of particulate exposure in asthma. Annals of the American Thoracic Society. 2018, 15(Supplement-2): S129. PubMed ID: 29676619
   
   

   The study indicates that the changes in CysLTR1 expression and methylation of CpG sites on CysLTR1 and leukotriene C4 synthase genes are associated with health effects of acute particulate exposure on asthma.

2. Hu C., et al. CysLTR1 blockage ameliorates liver injury caused by aluminum-overload via PI3K/AKT/mTOR-mediated autophagy activation in Vivo and in Vitro. Molecular Pharmaceutics. 2018. 15(5): 1996-2006. PubMed ID: 29634275
   
   

   The study indicates that the inhibition of CysLTR1 promotes autophagy and further reduces hepatocyte death through inhibiting the PI3K/AKT/mTOR pathway. Hence CysLTR1 could act as a potential target for the new drug development for chronic noninfective liver injury.

3. Song W., et al. Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast suppresses cell senescence of chondrocytes. Cytokine. 2018, 103: 83-89. PubMed ID: 29331588
   
   

   The study shows that cysLTR1 can regulate cellular senescence in chondrocytes. Montelukast, an antagonist of cysteinyl leukotriene receptor 1 can suppress cellular senescence in chondrocytes via regulating the expression of the senescence markers p53, p21 and PAI-1, as well as inhibiting TNF-α-induced K382 acetylation of p53.

4. Osman J., et al. Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of colitis-associated colon cancer. Oncotarget. 2017, 8(21): 34773-34786. PubMed ID: 28410235
   
   

   The study shows that azoxymethane/dextran sulfate sodium (AOM/DSS) female mice with Cysltr1^-/- have a higher relative body weight, a more normal weight/length colon ratio and smaller-sized colonic polyps compared to AOM/DSS wild-type counterparts. And Cysltr1^-/- mice exhibit an overall reduction in inflammation, with a significant decrease in proinflammatory cytokines.

5. Mcgovern T., et al. CysLT1 receptor is protective against oxidative stress in a model of irritant-induced asthma. Journal of Immunology. 2016, 197(1): 266-77. PubMed ID: 27226094
   
   

   The study shows that the deficiency of cysLT1R could lead to an aberrant antioxidant response and increase the risk of oxidative injury. These suggest that cysLT1R is a protective factor to suppress oxidative stress in a model of irritant-induced asthma.

CYSLTR1 Preparation Options

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Reference

1. Wisastra R and Dekker FJ. (2014). Inflammation, cancer and oxidative lipoxygenase activity are intimately linked. Cancers. 6(3), 1500-21.

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